Background: Human inter-α-trypsin inhibitor heavy chain 4 (ITIH4) is an acute phase response protein that is positively regulated by interleukin-6 (IL-6), suggesting that ITIH4 can be used as an early serological biomarker of gastric cancer.
Methods: The mechanism of ITIH4 elevation in gastric cancer cells was investigated via Helicobacter pylori (H. pylori) with or without recombinant human interleukin-6 (rhIL-6) in human gastric cell line AGS cells. The messenger RNA (mRNA) expressions of ITIH4 and IL-6 in AGS cells were detected with real-time quantitative polymerase chain reaction (qPCR), while the expression of ITIH4 protein and IL-6 in AGS cells was detected with Western blot and enzyme-linked immunosorbent assay (ELISA) methods.
Results: We found that the mRNA and protein expressions of ITIH4 started to increase synchronously at 3 hours (h), peaked at 12 h, and then declined to normal a level at 24 h in AGS cells after H. pylori infection. Interestingly, the expression patterns of ITIH4 were positively correlated to IL-6 expression levels. In the ITIH4 expression experiment with IL-6 administration, the expression level of ITIH4 began to increase at a concentration of 6.25 ng/mL with rhIL-6 administration, reach a peak, and plateau at a concentration of 25 ng/mL of rhIL-6. The expression patterns of ITIH4 in AGS cells induced by H. pylori infection were closely related to the infection of H. pylori and the level of IL-6.
Conclusions: The detection of ITIH4 and IL-6 during H. pylori infection may be useful for the screening of early gastric cancer.
Keywords: Gastric cancer; Helicobacter pylori (H. pylori); human inter-α-trypsin inhibitor heavy chain 4 (ITIH4); interleukin-6 (IL-6).
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